The goal of this project is to define the mechanisms by which T-cell surface molecules function in the recognition of foreign cell surface molecules. A large panel of SB-specific cytotoxic T-cell (CTL) clones have been developed to facilitate the study of membrane molecules that are involved in T-cell recognition and triggering. These CTL clones have been used to analyze the roles of the T3 and T4 surface molecules in T-cell recognition of the class II MHC antigens. The results suggest that the role of the T4 molecule may be to facilitate T-cell recognition of class II molecules by binding to a nonpolymorphic region of the molecule and thereby increasing the overall tightness of binding of T-cells to target cells. This hypothesis is being tested by an assay that was developed to quantitatively measure the avidity of individual T-cell clones for target cells. A model for T-cell recognition is proposed in which the antigen-specific receptor determines the fine specificity and affinity of antigen recognition and the T4 molecule provides the ancillary function of increasing the overall avidity of T-cell interactions with cells bearing class II MHC molecules. Studies are also conducted on the functional role of the T8 molecule. The T8 molecule is pedominantly expressed on T-cells that have specificity for class I MHC molecules. Some monoclonal antibodies to the T8 molecule block CTL function of T8-positive cells. We are analyzing the role of particular epitopes of the T8 molecule in CTL function by utilizing a panel of anti-T8 monoclonal antibodies directed to distinct non-overlapping epitopes. The results indicated that specific epitopes on the T8 molecule are involved in CTL function, and that there could be more than one functional site on the molecule.